Methyl gallate

The crystal structure of the title compound (systematic name: methyl 3,4,5-trihydroxy­benzoate), C₈H₈O₅, is composed of essentially planar mol­ecules [maximum departures from the mean carbon and oxygen skeleton plane of 0.0348 (10) Å]. The H atoms of the three hydroxyl groups, which function as hydrogen-bond donors and acceptors simultaneously, are oriented in the same direction around the aromatic ring. In addition to two intra­molecular hydrogen bonds, each mol­ecule is hydrogen bonded to six others, creating a three-dimensional hydrogen-bonded network.

Key indicators

• Single-crystal X-ray study
• T = 100 K, P = 0.0 kPa
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.033
• wR factor = 0.093
• Data-to-parameter ratio = 11.2

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT029_ALERT_3_B _diffrn_measured_fraction_theta_full Low .......       0.95

Alert level C
GOODF01_ALERT_2_C  The least squares goodness of fit parameter lies
            outside the range 0.80 <> 2.00
            Goodness of fit given =      0.689
REFLT03_ALERT_3_C  Reflection count < 95% complete
           From the CIF: _diffrn_reflns_theta_max           66.97
           From the CIF: _diffrn_reflns_theta_full          66.97
           From the CIF: _reflns_number_total               1352
           TEST2: Reflns within _diffrn_reflns_theta_max
           Count of symmetry unique reflns         1428
           Completeness (_total/calc)             94.68%
PLAT022_ALERT_3_C Ratio Unique / Expected Reflections too Low ....       0.95
PLAT153_ALERT_1_C The su's on the Cell Axes   are Equal (x 100000)         20 Ang.

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   4 ALERT level C = Check and explain
   0 ALERT level G = General alerts; check

   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   1 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Gallic acid methyl ester (I) is a polyphenolic compound present in grape seeds and other natural substrates (Saxena et al., 1994; Schmidt et al., 2003; Hawas, 2007). Like other polyphenols, I shows antioxidant activity (Aruoma et al., 1993; Schmidt et al., 2003; Hawas, 2007). Formerly used as an astringent and in opthalmology, its anticancer (Fiuza et al., 2004) and antimicrobial properties (Saxena et al., 1994; Landete et al., 2007) have also been studied. The molecular structure of I is shown below.

The molecular geometry is as expected from chemical bond rules (Figure 1) and it shows an almost planar conformation, with maximum departures from the mean carbon and oxygen skeleton plane of 0.0343 (9) and 0.0348 (10) Å for O4 and C8, respectively. The relative positions of the carbonyl and the three hydroxyls were also observed in a cocrystal of I and 5-chloro-2-methyl-4-isothiazoline-3-one (Sekine et al., 2003). Four other compounds containing a gallic acid ester moiety have crystallized in an analogous conformation (Parkin et al., 2002; Okabe & Kyoyama, 2002a; Nomura et al., 2000; Mizuguchi et al., 2005). Three other planar conformations of gallic acid esters are found in the Cambridge Structural Database (Allen, 2002). I has one of these other conformations in a cocrystal with caffeine (Martin et al., 1986).

Crystallized I has intra- and intermolecular hydrogen bonding. The hydroxyl H atoms bound to O3 and O4 (donors) form intramolecular hydrogen bonds to O4 and O5 (acceptors), respectively. This is shown in Figure 1. Similar hydroxyl arrangements have been reported in other gallic acid derivatives, such as gallate ester solvates (Hitachi et al., 2005), a gallic acid monohydrate polymorph (Okabe et al., 2001) and 2,3,4-trihydroxybenzophenone monohydrate (Okabe & Kyoyama, 2002b).

Gallic acid methyl ester forms a three-dimensional H-bonded network lacking significant aromatic ring stacking interactions. There is one molecule of I in the asymmetric unit. The H-bonded network is shown in Figure 2. Using the carbonyl ester oxygen O1 (acceptor) and the hydroxyl O3 and O4 (donors), each molecule is linked to another four through two O1···H3—O3, and two O1···H4—O4 H-bonds. These H-bonds are likely relatively weak due to the spacial orientation of the H atoms with respect to the lone electron pairs of O1. In addition, there are two other O5—H5···O3 H-bonds. The three hydroxyl sites are used as hydrogen bond donors and acceptors simultaneously. In the ester group, only the carbonyl oxygen is used as an H-bond acceptor.

Related literature

For natural extracts containing gallic acid methyl ester, see: Saxena et al. (1994); Schmidt et al. (2003); Hawas (2007). For studies concerning antioxidant activity, see: Aruoma et al. (1993); Schmidt et al. (2003); Hawas (2007). For studies concerning anticancer properties, see: Fiuza et al. (2004) and for antimicrobial properties, see: Saxena et al. (1994); Landete et al. (2007). For cocrystals containing gallic acid methyl ester, see: Sekine et al. (2003); Martin et al. (1986). Similar gallate ester conformations are found in Parkin et al. (2002); Okabe & Kyoyama (2002a); Nomura et al. (2000); Mizuguchi et al. (2005). For structures with similar hydroxyl arrangements, see: Hitachi et al. (2005); Okabe et al. (2001); Okabe & Kyoyama (2002b). For a description of the Cambridge Structural Database, see: Allen (2002).

S2. Experimental

Gallic acid methyl ester was commercially obtained from Sigma-Aldrich (98% purity) and used as received. The crystal structure determination was carried out from a crystal with rhombic prismatic habit selected from the powder.

S3. Refinement

All hydrogen atoms were observed in the Fourier difference map. However, the torsion angle for the hydroxyl H was refined from the electron density and the methyl H was positioned in idealized staggered geometry. The H atoms were refined constrained to ride on their parent C or O atoms, with U_iso(H)=1.2 U_eq(C) for aromatic H, and U_iso(H)=1.5 U_eq(C or O) for methyl and hydroxyl H, respectively.

Computing details

Data collection: APEX2 (Bruker , 2004); cell refinement: SAINT-Plus (Bruker, 2004); data reduction: SAINT-Plus (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: WinGX (Farrugia, 1999); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2006); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures

	Fig. 1. Thermal ellipsoid plot of gallic acid methyl ester with the atomic numbering scheme. Non-H atoms are represented at 50% probability level. Intramolecular hydrogen bonds are shown with dashed lines.
	Fig. 2. The packing of gallic acid methyl ester molecules along the a-axis showing the unit cell and the hydrogen bonded network formed (dashed lines). Symmetry codes: (i) x,y,z; (ii) 1/2 + x, 1.5 - y, -1/2 + z; (iii) -1/2 + x, 1.5 - y, 1/2 + z; (iv) -1/2 + x,1.5 - y, -1/2 + z; (v) -1/2 - x, -1/2 + y, 1.5 - z; (vi) 1/2 + x, 1.5 - y, 1/2 + z; (vii) -1/2 - x, 1/2 + y, 1.5 - z.

methyl 3,4,5-trihydroxybenzoate

Crystal data

C8H8O5	F(000) = 384
Mr = 184.14	Dx = 1.526 Mg m^−3
Monoclinic, P21/n	Melting point: 474 K
Hall symbol: -P 2yn	Cu Kα radiation, λ = 1.54178 Å
a = 7.6963 (2) Å	Cell parameters from 1352 reflections
b = 9.9111 (2) Å	θ = 6.1–67.0°
c = 10.5625 (2) Å	µ = 1.12 mm^−1
β = 95.993 (1)°	T = 100 K
V = 801.29 (3) Å^3	Rhombic prism, colourless
Z = 4	0.31 × 0.23 × 0.21 mm

Data collection

Bruker SMART APEXII CCD diffractometer	1352 independent reflections
Radiation source: fine-focus sealed tube	1311 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.034
ω and ψ scans	θmax = 67.0°, θmin = 6.1°
Absorption correction: numerical (SADABS; Sheldrick, 2004)	h = −8→9
Tmin = 0.723, Tmax = 0.799	k = −11→11
8192 measured reflections	l = −12→12

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.033	Hydrogen site location: difference Fourier map
wR(F^2) = 0.093	All H-atom parameters refined
S = 0.69	w = 1/[σ^2(Fo^2) + (0.0834P)^2 + 0.9466P] where P = (Fo^2 + 2Fc^2)/3
1352 reflections	(Δ/σ)max = 0.004
121 parameters	Δρmax = 0.23 e Å^−3
0 restraints	Δρmin = −0.20 e Å^−3
32 constraints

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.14003 (11)	1.05605 (9)	0.77633 (8)	0.0145 (2)
O2	0.29090 (12)	0.99023 (9)	0.61631 (8)	0.0156 (3)
O3	−0.38148 (12)	0.74067 (10)	0.72722 (9)	0.0189 (3)
H3	−0.4389	0.6742	0.6963	0.028*
O4	−0.33530 (12)	0.58249 (9)	0.52444 (9)	0.0167 (2)
H4	−0.314	0.5462	0.4559	0.025*
O5	−0.05442 (13)	0.61740 (10)	0.39075 (9)	0.0185 (3)
H5	0.0127	0.6524	0.3422	0.028*
C7	0.15489 (17)	0.98352 (13)	0.68447 (12)	0.0121 (3)
C1	0.02736 (17)	0.87858 (13)	0.63777 (12)	0.0126 (3)
C2	−0.11958 (17)	0.85957 (13)	0.70290 (12)	0.0126 (3)
H2	−0.1378	0.9145	0.774	0.015*
C3	−0.23803 (17)	0.75983 (13)	0.66260 (12)	0.0129 (3)
C4	−0.21306 (17)	0.67861 (13)	0.55808 (12)	0.0129 (3)
C5	−0.06683 (17)	0.69987 (13)	0.49284 (12)	0.0134 (3)
C6	0.05370 (16)	0.79838 (13)	0.53249 (12)	0.0134 (3)
H6	0.1539	0.8116	0.4885	0.016*
C8	0.42258 (18)	1.09026 (14)	0.65644 (13)	0.0182 (3)
H8A	0.5161	1.0867	0.6003	0.027*
H8B	0.4712	1.0715	0.7441	0.027*
H8C	0.3695	1.1802	0.6521	0.027*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0147 (5)	0.0147 (5)	0.0141 (5)	0.0011 (4)	0.0010 (4)	−0.0023 (4)
O2	0.0135 (5)	0.0186 (5)	0.0153 (5)	−0.0048 (4)	0.0040 (4)	−0.0030 (4)
O3	0.0171 (5)	0.0206 (5)	0.0209 (5)	−0.0067 (4)	0.0108 (4)	−0.0070 (4)
O4	0.0188 (5)	0.0180 (5)	0.0141 (5)	−0.0071 (4)	0.0058 (4)	−0.0043 (4)
O5	0.0237 (5)	0.0196 (5)	0.0140 (5)	−0.0080 (4)	0.0103 (4)	−0.0057 (4)
C1	0.0135 (6)	0.0127 (6)	0.0114 (6)	0.0019 (5)	0.0004 (5)	0.0028 (5)
C2	0.0147 (7)	0.0130 (6)	0.0104 (6)	0.0023 (5)	0.0021 (5)	−0.0002 (5)
C3	0.0127 (6)	0.0147 (6)	0.0120 (6)	0.0012 (5)	0.0041 (5)	0.0025 (5)
C4	0.0137 (6)	0.0123 (6)	0.0124 (6)	−0.0012 (5)	0.0000 (5)	0.0022 (5)
C5	0.0176 (7)	0.0129 (6)	0.0100 (6)	0.0012 (5)	0.0032 (5)	0.0002 (5)
C6	0.0127 (6)	0.0159 (7)	0.0121 (6)	0.0004 (5)	0.0040 (5)	0.0024 (5)
C7	0.0129 (7)	0.0122 (6)	0.0111 (6)	0.0037 (5)	0.0006 (5)	0.0030 (5)
C8	0.0157 (7)	0.0203 (7)	0.0185 (7)	−0.0071 (5)	0.0015 (6)	−0.0010 (5)

Geometric parameters (Å, º)

O1—C7	1.2225 (16)	C1—C6	1.3988 (19)
O2—C7	1.3327 (15)	C2—C3	1.3815 (18)
O2—C8	1.4491 (16)	C2—H2	0.95
O3—C3	1.3705 (15)	C3—C4	1.3957 (18)
O3—H3	0.84	C4—C5	1.3956 (18)
O4—C4	1.3598 (16)	C5—C6	1.3813 (18)
O4—H4	0.84	C6—H6	0.95
O5—C5	1.3644 (16)	C8—H8A	0.98
O5—H5	0.84	C8—H8B	0.98
C7—C1	1.4790 (19)	C8—H8C	0.98
C1—C2	1.3965 (17)
C7—O2—C8	116.16 (10)	O4—C4—C5	123.25 (11)
C3—O3—H3	109.5	O4—C4—C3	117.52 (11)
C4—O4—H4	109.5	C5—C4—C3	119.22 (12)
C5—O5—H5	109.5	O5—C5—C6	124.25 (11)
O1—C7—O2	122.91 (12)	O5—C5—C4	115.24 (12)
O1—C7—C1	124.36 (11)	C6—C5—C4	120.51 (11)
O2—C7—C1	112.72 (11)	C5—C6—C1	119.62 (12)
C2—C1—C6	120.47 (12)	C5—C6—H6	120.2
C2—C1—C7	118.29 (11)	C1—C6—H6	120.2
C6—C1—C7	121.24 (12)	O2—C8—H8A	109.5
C3—C2—C1	119.15 (12)	O2—C8—H8B	109.5
C3—C2—H2	120.4	H8A—C8—H8B	109.5
C1—C2—H2	120.4	O2—C8—H8C	109.5
O3—C3—C2	119.06 (11)	H8A—C8—H8C	109.5
O3—C3—C4	119.91 (12)	H8B—C8—H8C	109.5
C2—C3—C4	121.03 (12)
C8—O2—C7—O1	−0.42 (18)	C2—C3—C4—O4	179.88 (11)
C8—O2—C7—C1	−179.68 (10)	O3—C3—C4—C5	179.65 (11)
O1—C7—C1—C2	−0.53 (19)	C2—C3—C4—C5	−0.7 (2)
O2—C7—C1—C2	178.71 (11)	O4—C4—C5—O5	0.45 (19)
O1—C7—C1—C6	−179.44 (12)	C3—C4—C5—O5	−178.97 (11)
O2—C7—C1—C6	−0.19 (17)	O4—C4—C5—C6	−179.37 (11)
C6—C1—C2—C3	0.47 (19)	C3—C4—C5—C6	1.21 (19)
C7—C1—C2—C3	−178.44 (11)	O5—C5—C6—C1	179.28 (12)
C1—C2—C3—O3	179.52 (11)	C4—C5—C6—C1	−0.92 (19)
C1—C2—C3—C4	−0.17 (19)	C2—C1—C6—C5	0.07 (19)
O3—C3—C4—O4	0.19 (18)	C7—C1—C6—C5	178.95 (11)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3···O4	0.84	2.25	2.7075 (13)	115
O4—H4···O5	0.84	2.29	2.7247 (12)	112
O4—H4···O1^i	0.84	2.15	2.9470 (13)	159
O3—H3···O1^ii	0.84	1.99	2.7007 (12)	142
O5—H5···O3^iii	0.84	1.86	2.6859 (12)	166

Symmetry codes: (i) x−1/2, −y+3/2, z−1/2; (ii) −x−1/2, y−1/2, −z+3/2; (iii) x+1/2, −y+3/2, z−1/2.